糖尿病肾病患者血清Wnt5a水平变化及其影响因素分析

Change of serum Wnt5a levels and analysis of influencing factors in patients with diabetic kidney disease

目的观察糖尿病肾病患者血清无翅型MMTV整合位点家族成员5a(Wnt5a)水平变化,并分析Wnt5a水平的影响因素。方法选择糖尿病肾病患者100例,根据尿白蛋白与肌酐比值(UACR),将患者分为微量白蛋白尿组(UACR 30~300 mg/g)和大量白蛋白尿组(UACR>300 mg/g)各50例;另选择UACR<30 mg/g的2型糖尿病患者50例作为对照组。采集三组空腹静脉血,采用ELISA法检测血清Wnt5a、转化生长因子β_(1)(TGF-β_(1))、白细胞介素6(IL-6)、肿瘤坏死因子α(TNF-α),采用葡萄糖氧化酶法检测空腹血糖(FPG),高压液相层析法检测糖化血红蛋白(HbA_(1c)),全自动生化仪检测总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)及低密度脂蛋白胆固醇(LDL-C),化学发光法检测空腹胰岛素(FINS),计算稳态模型评估胰岛素抵抗指数(HOMA-IR)。采用Pearson相关分析法分析血清Wnt5a与炎症因子、血糖、血脂及HOMA-IR的相关性,采用多元线性回归分析血清Wnt5a的影响因素。结果微量白蛋白尿组、大量白蛋白尿组血清Wnt5a水平高于对照组,且大量白蛋白尿组高于微量白蛋白尿组(P均<0.05)。与对照组相比,大量白蛋白尿组、微量白蛋白尿组HbA_(1c)、TC、TGF-β_(1)、IL-6、TNF-α升高,大量白蛋白尿组FPG、HOMA-IR、LDL-C升高(P均<0.05);与微量白蛋白尿组相比,大量白蛋白尿组HbA_(1c)、TC、TGF-β_(1)、IL-6、TNF-α升高(P均<0.05)。相关性分析显示,血清Wnt5a与TGF-β_(1)、IL-6、TNF-α、HbA_(1c)、FPG、HOMA-IR、TC、LDLC、UACR均呈正相关(r分别为0.575、0.544、0.580、0.691、0.631、0.660、0.541、0.535、0.625,P均<0.01)。多元回归分析显示,UACR、HOMA-IR是血清Wnt5a的影响因素。结论糖尿病肾病患者血清Wnt5a水平较不合并肾脏病的糖尿病患者明显升高,且Wnt5a水平与炎症因子、血糖、血脂及胰岛素抵抗水平有关。

Objective To observe the changes of serum wingless-type MMTV integration site family member 5a(Wnt5a)levels in patients with diabetic kidney disease(DKD),and to analyze the influencing factors for Wnt5a levels.Methods A total of 100 patients with type 2 diabetes mellitus(T2DM)complicated with kidney disease were divided into the microalbuminuria group(UACR 30-300 mg/g)of 50 cases and macroalbuminuria group(UACR>300 mg/g)of 50 cases;50 cases of T2DM patients with UACR<30mg/g were selected as the control group.Fasting venous blood was collected from three groups,the levels of serum Wnt5a,transforming growth factor(TGF)-β_(1),interleukin(IL)-6,and tumor necrosis factor(TNF)-αwere detected by ELISA.Fasting blood glucose(FPG)was detected by glucose oxidase method,and glycosylated hemoglobin(HbA_(1c)) was detected by high pressure liquid chromatography.Total cholesterol(TC),triglyceride(TG),high-density lipoprotein cholesterol(HDL-C),and low-density lipoprotein cholesterol(LDL-C)were detected by automatic biochemical analyzer.Fasting insulin(FINS)level was measured by chemiluminescence.Homeostasis model assessment for insulin resistance(HOMA-IR)was computed.Pearson correlation analysis was used to analyze the correlations between serum Wnt5a and inflammatory factors,blood glucose,blood lipid and HOMA-IR.Multiple linear regression was used to analyze the influencing factors for serum Wnt5a.Results The levels of serum Wnt5a in the microalbuminuria group and macroalbuminuria group were higher than those in the control group,and that was higher in the macroalbuminuria group than in the microalbuminuria group(all P<0.05).Compared with the control group,HbA_(1c),TC,TGF-β_(1),IL-6,and TNF-αsignificantly increased in the macroalbuminuria group and microalbuminuria group(all P<0.05),and FPG,HOMA-IR and LDL-C significantly increased in the macroalbuminuria group(all P<0.05).Compared with the microalbuminuria group,HbA_(1c),TC,TGF-β_(1),IL-6 and TNF-αsignificantly increased in the macroalbuminuria group(all P<0.05).Correlation analysis showed that the levels of serum Wnt5a were positively correlated with TGF-β_(1),IL-6,TNF-α,HbA_(1c),FPG,HOMA-IR,TC,LDL-C,and UACR(r=0.575,0.544,0.580,0.691,0.631,0.660,0.541,0.535,and 0.625,all P<0.05).Multiple linear regression analysis showed that UACR and HOMA-IR were independent influencing factors for serum Wnt5a.Conclusions The levels of serum Wnt5a in diabetic nephropathy patients were significantly higher than those in diabetic patients without kidney disease,and were closely related to inflammatory factors,blood glucose,blood lipid,and insulin resistance.